Key issues in the selection of an expression system for vaccine antigens

Ellis, Ronald W.; Gerety, Robert J.

doi:10.1002/jmv.1890310111

Cited by 10 publications

(5 citation statements)

References 8 publications

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“…are used for the production of complex assembled glycoproteins such as antibodies. Production based on mammalian cells, like Chinese Hamster Ovary (CHO) cells is straightforward for the production of mAbs but is complicated, expensive and often associated with the risk of animalderived products when synthetic fusions need to be produced [14][15][16]. Therefore, transgenic plants and yeast expression systems show a great potential.…”

Section: Introductionmentioning

confidence: 99%

Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium

Bakshi

Garcia

Weken

et al. 2020

Journal of Controlled Release

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Targeting a vaccine to the mucosal surface has recently been recognized as a promising approach to efficiently induce mucosal immune responses against enteric pathogens. However, poor uptake and inefficient transport of orally delivered subunit vaccines across the intestinal epithelium combined with weak immune responses still present important bottlenecks for mucosal vaccination. A possible strategy suggested to surmount these hurdles is to target the selected antigen to transcytotic receptors, such as aminopeptidase N (APN) present on enterocytes and antigen-presenting cells (APCs). Therefore, we aimed to identify potent and selective VHHs against porcine aminopeptidase N (pAPN), that were fused to the fragment crystallizable (Fc) domain of the murine IgG2a, resulting in dimeric VHH-MG fusions. Out of a library of 30 VHH-2 MG fusion candidates, two fusions displaying the best binding on pAPN-expressing cells were selected and showed in vivo internalization across the porcine gut epithelium. One of these fusions triggered systemic and intestinal IgA responses upon oral administration. Our results demonstrate the potential of bivalent VHH-MG fusions as delivery vehicles for vaccine antigens. VHHmediated and APN-targeted antigens to generate protective immunity at the mucosal surface remains to be further validated.

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Section: Introductionmentioning

confidence: 99%

Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium

Bakshi

Garcia

Weken

et al. 2020

Journal of Controlled Release

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“…For example, bacteria can perform very few protein posttranslational modifications and therefore are typically used to produce recombinant proteins that do not require extensive posttranslational modifications for their biological activity (34). Bacterial products can also contain endotoxin (50). Yeasts are scalable and cost effective and, as eukaryotic organisms, are capable of folding and assembling mammalian proteins and performing both O-and N-linked glycosylation.…”

Section: Common Precursor: Man8mentioning

confidence: 99%

“…Mammalian cells perform a wide variety of posttranslational modifications, including N-glycosylation, and thus have been widely utilized to produce various soluble and complex recombinant proteins (73,208). However, production in mammalian cell systems bears potential safety risks, including product contamination with residual host cell-derived proteins, mammalian viruses, or mammalian DNA with oncogenic activity (50). Development of a heterologous platform that is safe, effective, and scalable would be highly desirable to address the market demand for mAbs and associated products for a wide variety of applications.…”

Section: Common Precursor: Man8mentioning

confidence: 99%

Antibody Production in Plants and Green Algae

Yusibov

Kushnir

Streatfield

2016

Annu. Rev. Plant Biol.

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Monoclonal antibodies (mAbs) have a wide range of modern applications, including research, diagnostic, therapeutic, and industrial uses. Market demand for mAbs is high and continues to grow. Although mammalian systems, which currently dominate the biomanufacturing industry, produce effective and safe recombinant mAbs, they have a limited manufacturing capacity and high costs. Bacteria, yeast, and insect cell systems are highly scalable and cost effective but vary in their ability to produce appropriate posttranslationally modified mAbs. Plants and green algae are emerging as promising production platforms because of their time and cost efficiencies, scalability, lack of mammalian pathogens, and eukaryotic posttranslational protein modification machinery. So far, plant- and algae-derived mAbs have been produced predominantly as candidate therapeutics for infectious diseases and cancer. These candidates have been extensively evaluated in animal models, and some have shown efficacy in clinical trials. Here, we review ongoing efforts to advance the production of mAbs in plants and algae.

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“…However, there are questions about the use of tumor-derived continuous cell lines (TCLs) for a preventive vaccine in a healthy population. [ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] There is no precedent to use such cell substrates in the manufacture of U.S. licensed preventive vaccines intended for healthy subjects. In addition to the need to demonstrate that the cells are free from adventitious agents detectable by the typical screening tests, concerns also arise from the possibility of tumorigenicity from four sources of contamination of the product by the cell substrate.…”

Section: Introductionmentioning

confidence: 99%

Workshop Report: Traditional Approach Preventive HIV Vaccines: What Are the Cell Substrate and Inactivation Issues?1

Sheets

Goldenthal²

1998

AIDS Research and Human Retroviruses

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A workshop was convened to discuss safety issues for traditional-approach HIV vaccines, especially inactivated vaccines. The topics included issues pertaining to (1) cell substrates used for production and (2) vaccine virus inactivation. The use of cell substrates such as tumor-derived continuous cell lines (TCLs) or virus-transformed. CLs may be the most feasible approach to provide commercial-scale virus yields. However, especially because of concerns about tumorigenicity, TCLs have not been used to produce preventive vaccines for human trials with healthy subjects in the United States. Residual TCL material (e.g., DNA, cellular proteins, viruses) may not be removed during purification of intact HIV virions to the same extent achievable for a recombinant protein. Manufacturing processes, e.g., physicochemical methods of destroying DNA, could decrease tumorigenicity risk. Methods to assess potential for tumorigenicity may need further development. Another potential substrate for viral production that merits further study is human peripheral blood mononuclear cells (PBMCs). Regardless of the cell substrate used, extensive testing for adventitious agents (including non-HIV retroviruses) is needed. Vaccine virus inactivation can be considered in statistical terms, i.e., the probability of a surviving infectious particle. One formula to determine a "safety margin" (SM) is reduction of titer in log10 for all inactivation steps minus initial viral infectivity in log10. Calculations for appropriate SMs should include all sources of variability (e.g., lot-to-lot differences). Ensuring a specified SM, as the lower bound of the 95% confidence interval, for production lots was discussed. Sensitivity and specificity of infectivity assays may present limitations.

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Key issues in the selection of an expression system for vaccine antigens

Cited by 10 publications

References 8 publications

Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium

Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium

Antibody Production in Plants and Green Algae

Workshop Report: Traditional Approach Preventive HIV Vaccines: What Are the Cell Substrate and Inactivation Issues?1

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